This grant application is for a VA Clinical Science Research and Development (CSR&D) Career Development Award (CDA-2) for Christine Lee, MD, MS. Her training goal is to become an independent clinical and translational researcher in the field of sarcopenia research. The career development plan includes the following learning objectives: (1) experience in the conduct and analysis of interventional clinical trials, (2) knowledge and research techniques in muscle physiology and (3) understanding of concepts and lab techniques for studying muscle biology. Dr. Lee will receive scientific and career guidance from an interdisciplinary mentorship team comprising epidemiologic, clinical and translational researchers with expertise in insulin resistance and musculoskeletal aging. Key didactic, clinical and laboratory resources at the Portland Veteran's Administration Medical Center, the Oregon Clinical and Translational Research Institute, the Department of Biochemistry and Molecular Biology and Bone and Mineral Unit at the Oregon Health & Science University, and the University of Pittsburgh will assist in Dr. Lee's training and completion of her research projects. The proposed study utilizes clinical and translational research approaches to not only provide Dr. Lee with opportunities to reach the career goals delineated above, but also to contribute to the field of sarcopenia research. Sarcopenia is associated with decreased strength, increased disability, more falls and fractures and is present in over 50% of U.S. adults past the age of 80. There are currently few interventions to prevent or treat sarcopenia and a poor understanding of the mechanisms for sarcopenia. Given the growing number of veterans over the age of 65, studies to prevent sarcopenia and resulting disability are important for the health, independence and well-being of this population. Dr. Lee's preliminary data showed that older men with impaired fasting glucose and diabetes had accelerated muscle loss, except when men with diabetes were treated with metformin. The scientific aims of this proposal further investigates this finding by attempting (1) to determine whether metformin can prevent the loss in muscle mass and physical performance and (2) to examine changes in muscle histologic characteristics associated with metformin treatment. The goal to understand mechanisms for preventing sarcopenia may lead to more effective methods for preserving function for the growing population of aging veterans. The addition of clinical and translational research skills for studying muscle will allow Dr. Lee to become a valuable member of the sarcopenia research community.